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HEALTH AND DRUG ALERTS
Reason for posting: Pioglitazone is an oral hypoglycemic agent widely used as monotherapy or combination therapy for type 2 diabetes mellitus. However, a recent analysis by the drug's manufacturer of several unpublished clinical trials in the company's database revealed an increased risk of bone fracture among pioglitazone users. Health Canada and the drug's manufacturer recently issued a letter warning health care professionals about this potential serious adverse effect.1
The drug: Pioglitazone is a thiazolidinedione (also known as a TZD, or "glitazone"). It binds to and activates peroxisome proliferator-activated receptors (PPAR), including the PPAR gamma and alpha subtypes. These receptors in turn increase glucose utilization and decrease glucose production by the liver, and increase insulin sensitivity in adipose and muscle tissue.
The Health Canada advisory1 was based on an unpublished, manufacturer- led review of double-blind randomized controlled trials of pioglitazone use in diabetic patients. Primary outcome measures in the trials included glycemic control, liver function and vascular events. The trials were not designed specifically to assess fracture risk, and fractures were recorded as adverse events. The doses of pioglitazone used are unclear. Participants in the comparison group were given either a placebo or another...